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| 1 | Influences of Ivabradine treatment on serum levels of cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in patients with chronic heart failure显示文摘长期的心失败(CHF ) 代表住院和死亡的一个主要原因。最近的证据表演那新奇 biomarkers 象 tumorigenicity (sST2 ) 的可溶的抑制那样,生长区别 factor-15 (GDF-15 ) ,可溶的尿激 plasminogen 使活跃之物受体(suPAR ) 和心类型丰满的酸绑定蛋白质(H-FABP ) 被相关与煽动性并且在 CHF 病人的 ischemic 回答。在这研究,我们检验了禁止了 激活hyperpolarization 的周期的核苷酸门隧道的 Ivabradine 的效果( HCN 隧道,也叫的滑稽电流我 从而导致选择心率减小的 f ),和改进的心肌的氧在心脏的 biomarkers sST2 上供应, GDF-15 ,在在 Jena 的大学医院的 50 个 CHF 病人的 suPAR 和 H-FABP 。病人们基于 CHF 的病原学被划分成三个组:扩大心肌症(DCM, n=20 ) , ischemic 心肌症(ICM, n=20 ) 并且高血压的心肌症(HCM, n=10 ) 。病人是管理 Ivabradine (5 mg,为 3 个月的出价,和 7.5 mg 期望推进 3 个月) 。心血管的 biomarkers 的分析在基线以及在 3 月、 6 月的后续被执行。在 6 月的后续, GDF-15 层次显著地与基线层次(P=0.0215 ) 相比被减少,显示在心脏的改变的进步的减小。H-FABP 集中在与 ICM (1.89 对 3.24 g/mL ) 和 HCM 病人(1.89 对 3.80 g/mL ) 相比的 DCM 病人是显著地更低的,并且在 6 月的后续(P=0.0151 ) 上减少了。中部的层次仍然是的 suPAR 提高了,暗示主要进行中的煽动性的过程。是在 GDF-15 和 H-FABP 由重要减少证明层次,在室的改变的减小和无临床症状的局部缺血能被假定。然而,血液动力学的应力(sST2 ) 的标记和发炎(suPAR ) 没在 CHF 病人在 6 月 Ivabradine 治疗以后显示出变化或前进。进一步的研究是必要的验证这些新奇心血管的 biomarkers 的临床的适用性。 | Peter JIRAK Dzeneta FEJZIC Vera PAAR Bernhard WERNLY Rudin PISTULLI Ilonka ROHM Christian JUNG Uta C HOPPE P Christian SCHULZE Michael LICHTENAUER Atilla YILMAZ Daniel KRETZSCHMAR | 2018 | Acta Pharmacologica Sinica2018，39，7： | 31 |
| 2 | Immunotherapy for hepatocellular carcinoma:Current and future显示文摘Hepatocellular carcinoma(HCC)arises on the background of chronic liver disease.Despite the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fatty liver disease.Many patients present with advanced disease out with the criteria for transplant,resection or even locoregional therapy.Currently available therapeutics for HCC are effective in a small minority of individuals.However,there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers,great opportunities now exist for treating HCC with newer and more sophisticated agents.Whilst checkpoint inhibitors are at the forefront of this revolution,other therapeutics such as inhibitory cytokine blockade,oncolytic viruses,adoptive cellular therapies and vaccines are emerging.Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response.Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy,either in combination with one another or in combination with treatment modalities such as locoregional therapy.Together these agents are likely to generate new and exciting opportunities for treating HCC,which are summarized in this review. | Michael P Johnston Salim I Khakoo | 2019 | World Journal of Gastroenterology2019，25，24： | 23 |
| 3 | The ReaxFF reactive force-field: development, applications and future directions显示文摘The reactive force-field(ReaxFF)interatomic potential is a powerful computational tool for exploring,developing and optimizing material properties.Methods based on the principles of quantum mechanics(QM),while offering valuable theoretical guidance at the electronic level,are often too computationally intense for simulations that consider the full dynamic evolution of a system.Alternatively,empirical interatomic potentials that are based on classical principles require significantly fewer computational resources,which enables simulations to better describe dynamic processes over longer timeframes and on larger scales.Such methods,however,typically require a predefined connectivity between atoms,precluding simulations that involve reactive events.The ReaxFF method was developed to help bridge this gap.Approaching the gap from the classical side,ReaxFF casts the empirical interatomic potential within a bond-order formalism,thus implicitly describing chemical bonding without expensive QM calculations.This article provides an overview of the development,application,and future directions of the ReaxFF method. | Thomas P Senftle Sungwook Hong Md Mahbubul Islam Sudhir B Kylasa Yuanxia Zheng Yun Kyung Shin Chad Junkermeier Roman Engel-Herbert Michael J Janik Hasan Metin Aktulga Toon Verstraelen Ananth Grama Adri CT van Duin | 2016 | npj Computational Materials2016，，1： | 22 |
| 4 | Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients显示文摘AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting cir-culating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P< 0.001) and preoperative serum levels of CEA (P=0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented signif icant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RTPCR assay can provide useful information concerning disease stage and overall survival of CRC patients. | Aikaterini Tsouma Chrysanthi Aggeli Panagiotis Lembessis George N Zografos Dimitris P Korkolis Dimitrios Pectasides Maria Skondra Nikolaos Pissimissis Anastasia Tzonou Michael Koutsilieris | 2010 | World Journal of Gastroenterology2010，16，47： | 19 |
| 5 | Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome显示文摘AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies. | Konstantinos Kargiotis Vasilios G Athyros Olga Giouleme Niki Katsiki Evangelia Katsiki Panagiotis Anagnostis Chrysoula Boutari Michael Doumas Asterios Karagiannis Dimitri P Mikhailidis | 2015 | World Journal of Gastroenterology2015，21，25： | 18 |
| 6 | Prediction of atrial fibrillation development and progression:current perspectives显示文摘Atrial fibrillation(AF) is the most common arrhythmia in clinical practice. Several conventional and novel predictors of AF development and progression(from paroxysmal to persistent and permanent types) have been reported. The most important predictor of AF progression is possibly the arrhythmia itself. The electrical, mechanical and structural remodeling determines the perpetuation of AF and the progression from paroxysmal to persistent and permanent forms. Common clinical scores such as the hypertension, age ≥ 75 years, transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure and the congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category scores as well as biomarkers related to inflammation may also add important information on this topic. There is now increasing evidence that even in patients with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a structural atrial disease which has recently been defined and described as fibrotic atrial cardiomyopathy. Fibrosis results from a broad range of factors related to AF inducing pathologies such as cell stretch, neurohumoral activation, and oxidative stress. The extent of fibrosis as detected either by late gadolinium enhancement-magnetic resonance imaging or electroanatomic voltage mapping may guide the therapeutic approach based on the arrhythmia substrate. The knowledge of these risk factors may not only delay arrhythmia progression, but also reduce the arrhythmia burden in patients with first detected AF. The present review highlights on the conventional and novel risk factors of development and progression of AF. | Konstantinos Vlachos Konstantinos P Letsas Panagiotis Korantzopoulos Tong Liu Stamatis Georgopoulos Athanasios Bakalakos Nikolaos Karamichalakis Sotirios Xydonas Michael Efremidis Antonios Sideris | 2016 | World Journal of Cardiology2016，8，3： | 16 |
| 7 | Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival显示文摘BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (<400 ng/ml) (Odds ratio=3.3) and PR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents. | Timm D Kirchhoff Joerg S Bleck Arne Dettmer Ajay Chavan Herbert Rosenthal Sonja Merkesdal Bernd Frericks Lars Zender Nisar P Malek Tim F Greten Stefan Kubicka Michael P Manns Michael Galanski | 2007 | Hepatobiliary & Pancreatic Diseases International2007，6，3： | 15 |
| 8 | Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma显示文摘瞄准:为病人评估经皮的乙醇注射(PEI ) 的治疗效果与先进, non-resectable HCC 与 transarterial chemoembolisation 的联合相比(不作声) 并且重复单个会议的 PEI,独自重复了单个会议的 PEI,重复不作声独自一个,或最好的支持的照顾。方法:在学习时期期间接受了 PEI 治疗的所有病人根据物理地位和肿瘤程度被包括并且成层到下列治疗形式之一:联合不作声并且重复单个会议的 PEI,独自重复了单个会议的 PEI,重复不作声独自一个,或最好的支持的照顾。包括Okuda分类,门静脉血栓的存在,腹水的存在,肿瘤的数字,最大的肿瘤直径,和假胆硷酯酶( CHE )的临床的参数的预示的价值,以及孩子呸上演, alpha-fetoprotein (法新社),发烧,复杂并发症的发生在这些组之间被估计并且比较。幸存用 Kaplan-Meier 被决定,多,变量回归分析。结果:所有病人的 1 年、 3 年的幸存是 73% 和 47% 。在亚群分析,联合不作声, PEI (1 ) 与更长的幸存被联系(1- , 3- , 5 年的幸存:90% , 52% ,和 43%) 与 PEI 治疗相比独自一个(2 )(1- , 3- , 5 年的幸存:65% , 50% ,和 37%) 。(3 ) 在起始的层化以后的第二等的 PEI 产出可比较的结果不作声(1- , 3- , 5 年的幸存:91% , 40% ,和 30%) 当在到最好的支持的照顾(4 ) 的层化以后的 PEI 与减少的幸存被联系时(1- , 3- , 5 年的幸存:50% , 23% , 12%) 。除了选择治疗形式,为更好的幸存的预言者是肿瘤数字(n <
5 ) ,肿瘤尺寸(<
5 厘米) ,在 PEI 前的没有腹水,和在 PEI 以后的稳定的假胆硷酯酶(P <
0.05 ) 。在在 PEI 以后的 2 wk 以内的死亡是 2.8%(n = 3 ) 。有 24 (8.9%) 主修在包括部分肝梗塞,焦点的肝坏死,和肝脓肿的 PEI 以后的复杂并发症。所有复杂并发症能非通过手术被管理。结论:重复单个会议的 PEI 在有以可接受、可管理的复杂并发症率的先进 HCC 的病人是有效的。病人们成层到联合不作声, PEI 能比那些独自成层到重复 PEI 期望更长的幸存。而且,有在好临床的地位的大或多重的肿瘤的病人可以也从联合获利不作声并且为第二等的 PEI 的再考虑。 | Arne Dettmer Timm D Kirchhoff Michael Gebel Lars Zender Nisar P Malek Bernhard Panning Ajay Chavan Herbert Rosenthal Stefan Kubicka Susanne Krusche Sonja Merkesdal Michael Galanski Michael P Manns Joerg S Bleck | 2006 | World Journal of Gastroenterology2006，12，23： | 14 |
| 9 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 10 | miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus显示文摘AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium. | Cameron M Smith David I Watson Mary P Leong George C Mayne Michael Z Michael Bas PL Wijnhoven Damian J Hussey | 2011 | World Journal of Gastroenterology2011，17，8： | 13 |
| 11 | Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma显示文摘瞄准:与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法:骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80, CD83, CD86 和 HLA 医生表示被分析。骨髓的的树枝状的房间从外部血被孤立,他们的功能被测试。吞噬作用用 FITC 葡聚糖祷告被分析,肽特殊刺激,在多形核白细胞 dI:dC 之上刺激 allogeneic T 房间和 cytokines 的分泌物的能力被测试。结果:骨髓的的树枝状的房间与 HCC 在病人被减少。在 CD80, CD83, CD86 和 HLA 医生表示的差别都没从 HCC 病人和健康控制在天真、刺激的骨髓的的树枝状的房间上被发现。肽 specific T 房间的正常吞噬作用或刺激与一个损害 allo-stimulatory 能力和减少的 IL-12 分泌物相对照被观察。结论:在病人的 mDCs 的损害 IL-12 生产能导致建议指导治疗可以提高的那 IL-12 的天真的 T 房间的一个损害 stimulatory 能力在 HCC 病人的肿瘤 specific 免疫者回答。 | Lars A Ormandy Anatol Frber Tobias Cantz Susanne Petrykowska Heiner Wedemeyer Monique Hrning Frank Lehner Michael P Manns Firouzeh Korangy Tim F Greten | 2006 | World Journal of Gastroenterology2006，12，20： | 12 |
| 12 | Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer显示文摘AIM: To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor (IGF-1R) tyro- sine kinase inhibitor (TKI) NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer (CRC). METHODS: Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet stain- ing were used for analysis of growth factor receptor pro- tein expression and detection of cell number changes, respectively. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydro- genase (LDH). The proportion of apoptotic cells was determined by quantifying the percentage of sub-G1 (hypodiploid) cells. Cell cycle status reflected by the DNA content of the nuclei was detected by flow cytometry. RESULTS: NVP-AEW541 dose-dependently inhibited the proliferation of colorectal carcinoma cell lines and primary cell cultures by inducing apoptosis and cell cycle arrest. Apoptosis was characterized by caspase-3 activa- tion and nuclear degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541-mediated cell cycle-related signaling involved the inactivation of Akt and extracellular signal-regulated kinase (ERK) 1/2, the upregulation of the cyclin-dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. Moreover, BAX was upregu- lated during NVP-AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LDH release showed that the antineoplastic effect of NVP-AEW541 was not due to general cytotoxicity of the compound. However, augmented antineoplastic effects were ob-served in combination treatments of NVP-AEW541 with either 5-FU, or the EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin. CONCLUSION: IGF-1R-TK inhibition is a promising novel approach for either mono- or combination treatment strategies of colorectal carcinoma and even for CRC che- moprevention. | Michael Hpfner Andreas P Sutter Alexander Huether Viola Baradari Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，35： | 10 |
| 13 | Systematic review of nutrition screening and assessment in inflammatory bowel disease显示文摘BACKGROUND Malnutrition is prevalent in inflammatory bowel disease (IBD). Multiple nutrition screening (NST) and assessment tools (NAT) have been developed for general populations, but the evidence in patients with IBD remains unclear. AIM To systematically review the prevalence of abnormalities on NSTs and NATs, whether NSTs are associated with NATs, and whether they predict clinical outcomes in patients with IBD. METHODS Comprehensive searches performed in Medline, CINAHL Plus and PubMed. Included: English language studies correlating NSTs with NATs or NSTs/NATs with clinical outcomes in IBD. Excluded: Review articles/case studies;use of body mass index/laboratory values as sole NST/NAT;age<16. RESULTS Of 16 studies and 1618 patients were included, 72% Crohn’s disease and 28% ulcerative colitis. Four NSTs (the Malnutrition Universal Screening Tool, Malnutrition Inflammation Risk Tool (MIRT), Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NRT) and Nutrition Risk Screening 2002 (NRS-2002) were significantly associated with nutritional assessment measures of sarcopenia and the Subjective Global Assessment (SGA). Three NSTs (MIRT, NRS-2002 and Nutritional Risk Index) were associated with clinical outcomes including hospitalizations, need for surgery, disease flares, and length of stay (LOS). Sarcopenia was the most commonly evaluated NAT associated with outcomes including the need for surgery and post-operative complications. The SGA was not associated with clinical outcomes aside from LOS. CONCLUSION There is limited evidence correlating NSTs, NATs and clinical outcomes in IBD. Although studies support the association of NSTs/NATs with relevant outcomes, the heterogeneity calls for further studies before an optimal tool can be recommended. The NRS-2002, measures of sarcopenia and developments of novel NSTs/NATs, such as the MIRT, represent key, clinically-relevant areas for future exploration. | Suqing Li Michael Ney Tannaz Eslamparast Ben Vandermeer Kathleen P Ismond Karen Kroeker Brendan Halloran Maitreyi Raman Puneeta Tandon | 2019 | World Journal of Gastroenterology2019，25，28： | 9 |
| 14 | 学校卫生人员预防儿童性虐待知识态度及教育状况显示文摘目的 了解学校卫生人员预防儿童性虐待知识态度及教育活动。 方法 对 74名来自 1 3个省、市、自治区的学校卫生人员进行了不记名问卷调查。结果 97.3%的被调查人员赞成学校开展预防儿童性侵犯教育 ;学校卫生人员对儿童性侵犯问题有所了解 ,但仍有近半数人员缺少预防儿童性侵犯基本知识 ,在 1 4名担任小学健康教育课的老师中 ,只有 3人回答给学生讲过人身体的隐私部位是不能随便被人看到和触摸的。比较多的被调查人员认为有关预防儿童性侵犯教育内容“人身体各部分的名称”“好的接触和坏的接触”“与他人交往原则”“安全注意事项”等应该从小学 1、2年级开始讲。 结论 大多数学校卫生人员对学校预防儿童性侵犯教育持支持态度 ;应重视小学预防儿童性侵犯的教育以及对学校卫生人员有关预防儿童性侵犯教育基本知识和技能的培训。 | 陈晶琦 Michael P Dunne 韩萍 | 2004 | 中国校医2004，18，6： | 9 |
| 15 | Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR:A systematic literature review显示文摘AIM:To review literature on efficacy and safety of octreotide-long-acting repeatable(LAR)used at doses higher than the Food and Drug Administration(FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors(NETs).METHODS:We searched Pub Med and Cochrane Library from 1998-2012,5 conferences(American Society of Clinical Oncology,Endocrine Society,European Neuroendocrine Tumor Society,European Society for Medical Oncology,North American Neuroendocrine Tumor Society)from 2000-2013 using Me SH and keyterms including neuroendocrine tumors,carcinoid tumor,carcinoma,neuroendocrine,and octreotide.Bibliographies of accepted articles were also searched.Two reviewers reviewed titles,abstracts,and full-length articles.Studies that reported data on efficacy and safety of≥30 mg/mo octreotide-LAR for NETs in human subjects,published in any language were included in the review.RESULTS:The search identified 1086 publications,of which 238 underwent full-text review(20 were translated into English);17 were included in the review.Studies varied in designs,subjects,octreotide-LAR regimens,and definition of outcomes.Eleven studies reported use of higher doses to control symptoms and tumor progression,although symptom severity and formal quality-of-life analysis were not quantitatively measured.Ten studies reported efficacy,describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo.Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression.Eight studies reported safety;there was no evidence of increased toxicity associated with doses of octreotide-LAR>30 mg/mo.CONCLUSION:As reported in this review,octreotide-LAR at doses>30 mg/mo is being prescribed for symptom and tumor control in NET patients.Furthermore,expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms. | Michael S Broder David Beenhouwer Jonathan R Strosberg Maureen P Neary Dasha Cherepanov | 2015 | World Journal of Gastroenterology2015，21，6： | 8 |
| 16 | Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9显示文摘RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant(Prx1Cre;Rbpjkf/f), Rbpjk mutant/Sox9 haploinsufficient(Prx1Cre;Rbpjkf/f;Sox9f/1),and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors. | Anat Kohn Timothy P Rutkowski Zhaoyang Liu Anthony J Mirando Michael J Zuscik Regis J O'Keefe Matthew J Hilton | 2015 | Bone Research2015，3，3： | 8 |
| 17 | Lesion-symptom mapping with NIHSS sub-scores in ischemic stroke patients显示文摘Background Lesion-symptom mapping(LSM)is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome.In clinical practice,patients are commonly evaluated using the National Institutes of Health Stroke Scale(NIHSS),an 11-domain clinical score to quantitate neurological deficits due to stroke.So far,LSM studies have mostly used the total NIHSS score for analysis,which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation.Thus,the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.Methods Employing a multivariate technique,LSM analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE trial.The NIHSS domains were grouped into six categories using two schemes.LSM was conducted for each category of the two groupings and the total NIHSS score.Results Sub-score LSMs not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive,specialised assessments.Conclusion These findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships,which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging. | Deepthi Rajashekar Matthias Wilms M Ethan MacDonald Serena Schimert Michael D Hill Andrew Demchuk Mayank Goyal Sean P Dukelow Nils Daniel Forkert | 2022 | Stroke & Vascular Neurology2022，7，2： | 7 |
| 18 | 如何设计高质量针刺临床研究:基于证据的专家共识显示文摘本针刺随机对照试验(Randomised controlled trials, RCT)专家共识是基于目前针刺试验面临的最普遍、最关键问题,由临床医生、研究人员、从事针灸和外科的临床试验专家、统计专家、临床流行病学和方法学专家以及患者组成的国际临床研究小组联合制订。该共识将有助于临床试验资助者、注册者以及期刊编辑等评估针刺RCT方案及研究结果的相关性、重要性和质量。 | 张誉清 焦睿珉 Claudia M Witt 劳力行 刘建平 Lehana Thabane Karen J Sherman Mike Cummings Dawn P Richards Eun-Kyung Anna Kim Tae-Hun Kim Myeong Soo Lee Michael E Wechsler Benno Brinkhaus Jun J Mao Caroline A Smith 岗卫娟 刘保延 刘志顺 刘岩 郑晖 吴佳霓 AloBSO Carrasco-Labra Mohit Bhandari Philip J Devereaux 景向红 Gordon Guyatt | 2022 | 英国医学杂志中文版2022，25，6： | 7 |
| 19 | Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer显示文摘瞄准:在肝细胞癌(HCC ) 检验导致 erlotinib 的生长抑制的内在的机制。方法:在基因表示的导致 Erlotinib 的改变用 cDNA 数组技术被评估;在蛋白质表示或蛋白质激活的变化用西方的弄污由于象 IGF-1-induced EGFR transactivation 一样的 erlotinib 治疗被调查。结果:Erlotinib 治疗禁止了 mitogen 激活和抄写(STAT ) 的激活的蛋白质(地图)-kinase 小径和信号变换器调停了表明哪个导致了调整由 cDNA 数组技术示威了的基因的 apoptosis 和房间周期的一个改变的表达式。象与象 Bcl-2, Bcl-X (L) 或 jun D 一样的 antiapoptotic 因素的一条下面规定联系的 caspases 和 gadds 一样的 proapoptotic 因素的 Overexpression 说明了让 erlotinib 的力量导致 apoptosis。支持 G1/S-transition 的房间周期管理者并且在 cyclin 依赖的激酶禁止者和 gadds 的表示上的 Downregulation 响应 erlotinib 贡献了 G1/G0-arrest 的正式就职。而且,我们显示了由 IGF-1-receptor 的调停 EGFR 的发信号的 transactivation 并且在受体受体十字谈话显示出 erlotinib 的禁止的效果。结论:我们的学习在 HCC 房间和 thus 使 EGFR-TK-inhibition 的行动的机制的理解清楚些可能便于 additively 或 synergistically 行动的联合治疗的设计。而且,我们对 erlotinib 处理作出回应的小径上的数据能在以后预言肿瘤的应答的海角到 EGFR-TKIs 是有用的。 | Alexander Huether Michael Hpfner Andreas P Sutter Viola Baradari Detlef Schuppan Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，32： | 7 |
| 20 | Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation显示文摘BACKGROUND:Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation(DDLT) and living donor liver transplantation(LDLT).LDLT is thought to be associated with higher rates of biliary complications,but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups.This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT.METHODS:This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography(ERCP) after liver transplantation.The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT.The response of anastomotic stricture to endoscopic therapy was also analyzed.RESULTS:A total of 362 patients underwent liver transplantation between 2003 and 2011,with 125 requiring ERCP to manage biliary complications.Thirty-three(9.9%) cases of DDLT and 8(27.6%) of LDLT(P=0.01) were found to have anastomotic stricture.When comparing DDLT and LDLT,there was no difference in the mean time to the development of anastomotic strictures(98±17 vs 172±65 days,P=0.11),likelihood of response to ERCP [22(66.7%) vs 6(75.0%),P=0.69],mean time to the resolution of anastomotic strictures(268±77 vs 125±37 days,P=0.34),and the number of ERCPs required to achieve resolution(3.9±0.4 vs 4.7±0.9,P=0.38).CONCLUSIONS:Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation.Anastomotic strictures occur more frequently in LDLT compared with DDLT,with equivalent endoscopic treatment response and outcomes for both groups. | Calvin HY Chan Fergal Donnellan Michael F Byrne Alan Coss Mazhar Haque Holly Wiesenger Charles H Scudamore Urs P Steinbrecher Alan A Weiss Eric M Yoshida | 2013 | Hepatobiliary & Pancreatic Diseases International2013，12，5： | 7 |
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